Artemisone
(Synonyms: 青蒿酮; Artemifone; BAY 44-9585) 目录号 : GC34475
Artemisone(Artemifone)是一种有效、半合成的抗疟疾剂，能够抑制多种P.falciparum，平均IC50值为0.83nM。
Cas No.:255730-18-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Artemisone (Artemifone) is a potent and semi-synthetic antimalarial, inhibits P. falciparum strains, with a mean IC50 of 0.83 nM[1]. IC50: 0.83 nM (P. falciparum)[1]
Artemisone inhibits 3D7 and K1 P. falciparum, with IC50s of 0.88±0.59 and 1.23±0.64 nM, respectively[1].
Artemisone is effectve at inhibiting the parasitaemia in the P. berghei NY susceptible strain, with an ED50 of 9.62 mg/kg via subcutaneous route and 11.67 mg/kg via oral administration[1].Artemisone (3, 1, 0.3 and 0.1 mg/kg, s.c.) in combination with ohter antimalarials has enhanced effect against the chloroquine-resistant line P. yoelii NS[1]
[1]. Vivas L, et al. Antimalarial efficacy and drug interactions of the novel semi-synthetic endoperoxide artemisone in vitro and in vivo. J Antimicrob Chemother. 2007 Apr;59(4):658-65.
| Cas No. | 255730-18-8 | SDF | |
| 别名 | 青蒿酮; Artemifone; BAY 44-9585 | ||
| Canonical SMILES | C[C@H]1[C@H](N2CCS(CC2)(=O)=O)O[C@@]3([H])[C@]45[C@@]([C@H](C)CC[C@]51[H])([H])CC[C@@](O3)(C)OO4 | ||
| 分子式 | C19H31NO6S | 分子量 | 401.52 |
| 溶解度 | DMSO : 130 mg/mL (323.77 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4905 mL | 12.4527 mL | 24.9054 mL |
| 5 mM | 0.4981 mL | 2.4905 mL | 4.9811 mL |
| 10 mM | 0.2491 mL | 1.2453 mL | 2.4905 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Artemisone uptake in Plasmodium falciparum-infected erythrocytes
Antimicrob Agents Chemother 2011 Feb;55(2):550-6.PMID:21135191DOI:10.1128/AAC.01216-10.
Artemisone is one of the most promising artemisinin derivatives in clinical trials. Previous studies with radiolabeled artemisinin and dihydroartemisinin have measured uptake in Plasmodium falciparum-infected erythrocytes. Uptake is much greater in infected than in uninfected erythrocytes, but the relative contributions of transport, binding, and metabolism to this process still await definition. In this study, we characterized mechanisms by which [(14)C]Artemisone is taken up into uninfected and P. falciparum-infected human erythrocytes in vitro. Radiolabeled Artemisone rapidly enters uninfected erythrocytes without much exceeding extracellular concentrations. Unlabeled Artemisone does not compete in this process. Radiolabeled Artemisone is concentrated greatly by a time- and temperature-dependent mechanism in infected erythrocytes. This uptake is abrogated by unlabeled Artemisone. In addition, the uptake of Artemisone into three subcellular fractions, and its distribution into these fractions, is examined as a function of parasite maturation. These data are relevant to an understanding of the mechanisms of action of this important class of drugs.
Artemisone demonstrates synergistic antiviral activity in combination with approved and experimental drugs active against human cytomegalovirus
Antiviral Res 2019 Dec;172:104639.PMID:31654672DOI:10.1016/j.antiviral.2019.104639.
We have recently shown that the artemisinin derivative Artemisone, which was screened against malaria in human clinical studies, is a potent inhibitor of human cytomegalovirus (HCMV). Here we evaluated the antiviral effect of Artemisone when employed in 2-drug combinations with approved and experimental anti-HCMV agents. Using the Chou-Talalay method, we found that in-vitro combination of Artemisone with cidofovir, brincidofovir, or with the HCMV UL97 inhibitor maribavir resulted in antiviral synergism and the combination of Artemisone with ganciclovir or with the viral terminase inhibitors letermovir and BDCRB resulted in moderate synergism. Importantly, the combination of Artemisone with maribavir demonstrated synergistic antiviral activity ex-vivo, in a clinically-relevant multicellular model of human placental tissues maintained in organ culture. Our findings provide the basis for the use of Artemisone in synergistically acting drug combinations, to enhance viral control and reduce antiviral drug toxicities.
In vitro skin permeation of Artemisone and its nano-vesicular formulations
Int J Pharm 2016 Apr 30;503(1-2):1-7.PMID:26930566DOI:10.1016/j.ijpharm.2016.02.041.
The artemisinin derivative Artemisone has antitumor activity. In particular when encapsulated in solid lipid nanoparticles (SLNs) and niosomes, it is active against human melanoma A-375 cells, although such formulations have a negligible effect on human keratinocyte cells. The aim here was to determine whether these formulations could enhance the topical delivery and skin permeation of Artemisone as a prelude to evaluating use of Artemisone and related compounds for melanoma treatment. In vitro skin permeation studies were conducted to determine the concentration of Artemisone delivered into the stratum corneum-epidermis and epidermis-dermis. Artemisone-SLNs delivered Artemisone into the stratum corneum-epidermis at significantly higher concentration (62.632 μg/mL) than the artemisone-niosomes (12.792 μg/mL). Neither of the controls delivered Artemisone into the stratum corneum-epidermis. In the epidermis-dermis, Artemisone (13.404 μg/mL) was only detected after application of the SLN formulation. Overall, the excellent topical delivery of Artemisone with the SLN formulation coupled with the intrinsic activity of formulated Artemisone confirms potential for use in treatment of melanoma.
The Artemiside-Artemisox-Artemisone-M1 Tetrad: Efficacies against Blood Stage P. falciparum Parasites, DMPK Properties, and the Case for Artemiside
Pharmaceutics 2021 Dec 3;13(12):2066.PMID:34959347DOI:10.3390/pharmaceutics13122066.
Because of the need to replace the current clinical artemisinins in artemisinin combination therapies, we are evaluating fitness of amino-artemisinins for this purpose. These include the thiomorpholine derivative artemiside obtained in one scalable synthetic step from dihydroartemisinin (DHA) and the derived sulfone Artemisone. We have recently shown that artemiside undergoes facile metabolism via the sulfoxide artemisox into Artemisone and thence into the unsaturated metabolite M1; DHA is not a metabolite. Artemisox and M1 are now found to be approximately equipotent with artemiside and Artemisone in vitro against asexual P. falciparum (Pf) blood stage parasites (IC50 1.5-2.6 nM). Against Pf NF54 blood stage gametocytes, artemisox is potently active (IC50 18.9 nM early-stage, 2.7 nM late-stage), although against the late-stage gametocytes, activity is expressed, like other amino-artemisinins, at a prolonged incubation time of 72 h. Comparative drug metabolism and pharmacokinetic (DMPK) properties were assessed via po and iv administration of artemiside, artemisox, and Artemisone in a murine model. Following oral administration, the composite Cmax value of artemiside plus its metabolites artemisox and Artemisone formed in vivo is some 2.6-fold higher than that attained following administration of Artemisone alone. Given that efficacy of short half-life rapidly-acting antimalarial drugs such as the artemisinins is associated with Cmax, it is apparent that artemiside will be more active than Artemisone in vivo, due to additive effects of the metabolites. As is evident from earlier data, artemiside indeed possesses appreciably greater efficacy in vivo against murine malaria. Overall, the higher exposure levels of active drug following administration of artemiside coupled with its synthetic accessibility indicate it is much the preferred drug for incorporation into rational new artemisinin combination therapies.
Controlled release of Artemisone for the treatment of experimental cerebral malaria
Parasit Vectors 2017 Mar 1;10(1):117.PMID:28249591DOI:10.1186/s13071-017-2018-7.
Background: Cerebral malaria (CM) is a leading cause of malarial mortality resulting from infection by Plasmodium falciparum. Treatment commonly involves adjunctive care and injections or transfusion of artemisinins. All artemisinins that are in current use are metabolized to dihydroxyartemisinin (DHA), to which there is already some parasite resistance. We used Artemisone, a derivative that does not convert to DHA, has improved pharmacokinetics and anti-plasmodial activity and is also anti-inflammatory (an advantage given the immunopathological nature of CM). Methods: We examined controlled Artemisone release from biodegradable polymers in a mouse CM model. This would improve treatment by exposing the parasites for a longer period to a non-toxic drug concentration, high enough to eliminate the pathogen and prevent CM. The preparations were inserted into mice as prophylaxis, early or late treatment in the disease course. Results: The most efficient formulation was a rigid polymer, containing 80 mg/kg Artemisone, which cured all of the mice when used as early treatment and 60% of the mice when used as a very late treatment (at which stage all control mice would die of CM within 24 h). In those mice that were not completely cured, relapse followed a latent period of more than seven days. Prophylactic treatment four days prior to the infection prevented CM. We also measured the amount of Artemisone released from the rigid polymers using a bioassay with cultured P. falciparum. Significant amounts of Artemisone were released throughout at least ten days, in line with the in vivo prophylactic results. Conclusions: Overall, we demonstrate, as a proof-of-concept, a controlled-sustained release system of Artemisone for treatment of CM. Mice were cured or if treated at a very late stage of the disease, depicted a delay of a week before death. This delay would enable a considerable time window for exact diagnosis and appropriate additional treatment. Identical methods could be used for other parasites that are sensitive to artemisinins (e.g. Toxoplasma gondii and Neospora caninum).